DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 47-66 are presently pending, as amended 10/5/23, and are considered herein.
Drawings
The drawings are objected to.
Figures 1-4, 7-23, 25-36, and 38-53 are executed with color.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 47-66 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for mice, does not reasonably provide enablement for any species of animal. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make/use the invention commensurate in scope with these claims.
Nature of the Invention
The invention is the nature of suicide gene therapy for cells, driven by the transcription optimized to the particular cell type which is undesired. The field of gene therapy, expression of genes, and suicide gene therapy is relatively complex.
Breadth of the Claims
The claims are broad for the treatment of any condition or disease in any subject, where the subject has a senescent kidney cells, by administering an LNP comprising an expression construct with a p16 promoter driving expression of a gene that reduces growth/survival of the scenescent kidney cell, thus treating the condition or disease in any subject (e.g., Claim 47), including humans (e.g., Claim 55). It is the examiner’s argument here that there is a disconnect for the range of diseases/disorders which can be treated, essentially the claims are to treating anything under the sun, by killing a senescent kidney cell, in a subject. Additionally, the killing of senescent kidney cells is argued to be reasonably predictable for mice only, and does not reasonably predict to other species, such as humans.
Further, this breadth of diseases/conditions is very broad. The specification teaches that it may be used to treat any disease or condition, associated with transcriptional machinery (Paragraph 9), and the claims, utilizing the p16 promoter, are indicated to be relevant to senescent kidney cells (e.g., paragraph 14). Further, it is taught that the promoter is associated with the disease (e.g., paragraph 12). And while there are many disorders/diseases taught, they always are linked to the transcriptional factors involved (e.g., paragraphs 41 and 46). All of this is written in open-ended language, but the p16 promoter is specifically linked only to the disease/condition of senescent cells (paragraph 97). Thus, while the claims are directed to any disease or condition, the specification seems to indicate that the disease/disorder is senescent cells.
Relative Skill in the Art
The skill in the art is that of a scientist or doctor with several experience in gene therapy and kidney cell senescence. It is argued that this factor is addressed in the prior art cited, as such is written to level of the Artisan in the field.
Direction or Guidance Presented
The specification teaches that p16 is expressed in senescent cells (e.g., paragraph 14), and specifically kidney cells (e.g., paragraph 14). Further it teaches the use of the vector, to obtain selective expression in the target cells of that promoter (i.e., p16), to deliver a transgene that causes death of the cell that it targets (e.g., paragraphs 97, et. seq.).
Presence of Absence of Working Examples
Critically, Example 3 of the specification (paragraphs 154-158) teaches IV administration of mice with an LNP comprising p14 FAST for fusion, and carrying a p16 promoter driven iCasp9 gene (for causing cell death), and thus, it transfects cells in general, but is expressed in p16-expressing cells, due to the promoter, being selective to those cells (paragraph 156). Subesequent to tail-vein injection (essentially IV administration), and administration of the CID, the p16+ cells undergo apoptosis (paragraph 156).
State of the Prior Art
The state of the prior art may be represented in van Deursen (2014) “The role of senescent cells in ageing”, Nature, 509: 439-446. Van Deursen teaches that it is generally thought that cell senescence has been viewed as mechanism to product against cancer, but recently has been thought to contribute to processes such as development, tissue repair, aging, and age-related disorders (e.g., ABSTRACT), thus, at the outset, it is clear that killing senescent cells does not treat cancer, one of the diseases encompassed. But in fact, the only thing it can treat is the tissue processes of the cells that are treated, which must be necessarily the kidney cells that are senescent, and thus, claims to the breadth of disorders/diseases encompassed is not predicted in the art. For example, treating diabetes would not be predicted from killing senescent kidney cells, as the disease is in, e.g., the islet cells, of the subject, not in the kidney cells. It should be noted that diabetes is taught in paragraph 41 of the specification. Additionally, any other disorder which is not senescent kidney cells could not be predicted efficacious (e.g., Alzheimer’s disease), as they have nothing to do with senescent kidney cells.
With regard to the translation of therapeutics from mice to humans, or for that matter, any other species, van Deursen teaches that it not clear that a mouse is a reliable model for recapitulating the physiological effects of senescent cell accumulation and clearance in humans (p. 444, col. 2, paragraph 4). This is because one prominent stressor, telomere attrition, is specific to humans, and may be responsible for higher level of senescence in humans (Id.). Such indicates that other species may have other important aspects, and one may be telomere attrition. Additionally, removal of high amounts of scenescent cells could have undesirable outcomes to human health by triggering atrophy and tissue dysfunction. Still further, mice models rely on targeting p16 positive cells for elimination, which probably represents only a subset of cells undergoing senescence. The effects of clearing p16- cells or all senescent cells remains to be determined. In addition, human and mouse cells differentially rely on p16 and p53 pathways, underscoring the need to carefully validate information from mice, before extrapolating to humans. Further, although the existence of multiple senescent cell subtypes offers the same challenges and opportunities, targeting each population separately might have other beneficial or detrimental effects. Id.
Still further, Baker, et al. (2011) “Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders”, Nature, 479: 232-237 is perhaps the first showing in the art, of the linkage of p16 to ageing scenescent cells, in mice. In their model, a transgenic mouse expresses iCasp8, in p16-expressing cells, and addition of the interacting drug, could remove the p16-expressing cells(ABSTRACT). Such is admitted to be a proof-of-principle, and may represent an avenue for developing therapy for treating or delaying age-related diseases and improving healthy human lifespan (p. 235, col. 2, paragraph 3). However, this is a long step from predicting therapy, it being simply a mechanism that has been identified.
From this, the Artisan could not reasonably predict that any disease could be treated, by culling senescent kidney cells, nor predict that it would work for any species beyond that of mouse, particularly in humans, as the issues are distinctly driven, for the cause of the senescence.
Quantity of Experimentation Needed
In order to enable the breadth of the claims then, the Artisan would have to experiment to identify, for any species, which diseases/disorders could be treated by the method, beyond that of killing senescent kidney cells in mice. Such amounts to undue experimentation as it is required for the vast majority of embodiments encompassed.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638